21-46324123-CG-C

Position:

• chr21-46324123-CG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000466474.6(PCNT):​c.-100del variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (54873 hom., cov: 0)
  • Exomes 𝑓: 0.82 (257758 hom.)
• Consequence: PCNT ENST00000466474.6 5_prime_UTR, NMD_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.905

Genes affected

PCNT (HGNC:16068): (pericentrin) The protein encoded by this gene binds to calmodulin and is expressed in the centrosome. It is an integral component of the pericentriolar material (PCM). The protein contains a series of coiled-coil domains and a highly conserved PCM targeting motif called the PACT domain near its C-terminus. The protein interacts with the microtubule nucleation component gamma-tubulin and is likely important to normal functioning of the centrosomes, cytoskeleton, and cell-cycle progression. Mutations in this gene cause Seckel syndrome-4 and microcephalic osteodysplastic primordial dwarfism type II. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 21-46324123-CG-C is Benign according to our data. Variant chr21-46324123-CG-C is described in ClinVar as [Benign]. Clinvar id is 340455.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNT	NM_006031.6			upstream_gene_variant		ENST00000359568.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNT	ENST00000359568.10			upstream_gene_variant		1	NM_006031.6	P2

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128393 AN: 151882 Hom.: 54824 Cov.: 0

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.891

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.844

GnomAD4 exome AF: 0.819 AC: 618592 AN: 755128 Hom.: 257758 Cov.: 0 AF XY: 0.816 AC XY: 321609 AN XY: 394276

Gnomad4 AFR exome AF: 0.919

Gnomad4 AMR exome AF: 0.808

Gnomad4 ASJ exome AF: 0.879

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.769

Gnomad4 NFE exome AF: 0.854

Gnomad4 OTH exome AF: 0.829

GnomAD4 genome AF: 0.845 AC: 128502 AN: 151998 Hom.: 54873 Cov.: 0 AF XY: 0.836 AC XY: 62094 AN XY: 74278

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.846

Alfa AF: 0.797 Hom.: 2302

Bravo AF: 0.851

Asia WGS AF: 0.671 AC: 2339 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microcephalic osteodysplastic primordial dwarfism Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs397802954; hg19: chr21-47744037;